Neuropathic pain is a type of chronic pain state caused by injury or disease to the nervous system. Annual medical spending due to pain has been estimated to be over $100 billion. Currently there are no medications available to prevent or cure this devastating disease condition. Hence, there is an urgent need to discover effective drugs to treat this chronic pain condition. A promising drug target for neuropathic pain is the cannabinoid CB2 receptor. In phase I of this proposal our focus will be on the optimization of our lead compound to discover one or more CB2 receptor agonists with high receptor affinity and selectivity. In order to distinguish between agonist and antagonist activity, analogs that bind effectively to the CB2 receptor, will be evaluated for their ability to stimulate [35S]GTP?S binding. Our specific goal is to develop one or more lead CB2 agonists that show good activity and efficacy in an animal model for neuropathic pain. If this goal is accomplished in Phase I, we will have a drug candidate for further development in Phase II. The long-term goal of this proposal is to develop a medication for neuropathic pain that is effective and without undesirable side effects. [unreadable] [unreadable] [unreadable]